Olive (<i>Olea europaea</i> L.) Seed as New Source of Cholesterol-Lowering Bioactive Peptides: Elucidation of Their Mechanism of Action in HepG2 Cells and Their Trans-Epithelial Transport in Differentiated Caco-2 Cells
The production of olive oil has important economic repercussions in Mediterranean countries but also a considerable impact on the environment. This production generates enormous quantities of waste and by-products, which can be exploited as new raw materials to obtain innovative ingredients and ther...
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MDPI AG
2024-01-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/16/3/371 |
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| author | Martina Bartolomei Jianqiang Li Anna Laura Capriotti Melissa Fanzaga Lorenza d’Adduzio Aldo Laganà Andrea Cerrato Nadia Mulinacci Lorenzo Cecchi Carlotta Bollati Carmen Lammi |
| author_facet | Martina Bartolomei Jianqiang Li Anna Laura Capriotti Melissa Fanzaga Lorenza d’Adduzio Aldo Laganà Andrea Cerrato Nadia Mulinacci Lorenzo Cecchi Carlotta Bollati Carmen Lammi |
| author_sort | Martina Bartolomei |
| collection | DOAJ |
| description | The production of olive oil has important economic repercussions in Mediterranean countries but also a considerable impact on the environment. This production generates enormous quantities of waste and by-products, which can be exploited as new raw materials to obtain innovative ingredients and therefore make the olive production more sustainable. In a previous study, we decided to foster olive seeds by generating two protein hydrolysates using food-grade enzymes, alcalase (AH) and papain (PH). These hydrolysates have shown, both in vitro and at the cellular level, antioxidant and antidiabetic activities, being able to inhibit the activity of the DPP-IV enzyme and modulate the secretion of GLP-1. Given the multifunctional behavior of peptides, both hydrolysates displayed dual hypocholesterolemic activity, inhibiting the activity of HMGCoAR and impairing the PPI of PCSK9/LDLR, with an IC<sub>50</sub> equal to 0.61 mg/mL and 0.31 mg/mL for AH and PH, respectively. Furthermore, both samples restored LDLR protein levels on the membrane of human hepatic HepG2 cells, increasing the uptake of LDL from the extracellular environment. Since intestinal bioavailability is a key component of bioactive peptides, the second objective of this work is to evaluate the capacity of AH and PH peptides to be transported by differentiated human intestinal Caco-2 cells. The peptides transported by intestinal cells have been analyzed using mass spectrometry analysis, identifying a mixture of stable peptides that may represent new ingredients with multifunctional qualities for the development of nutraceuticals and functional foods to delay the onset of metabolic syndrome, promoting the principles of environmental sustainability. |
| first_indexed | 2024-03-08T03:52:11Z |
| format | Article |
| id | doaj.art-d980c7a5fa894dc8934267ba2c50cd4e |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-08T03:52:11Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-d980c7a5fa894dc8934267ba2c50cd4e2024-02-09T15:19:44ZengMDPI AGNutrients2072-66432024-01-0116337110.3390/nu16030371Olive (<i>Olea europaea</i> L.) Seed as New Source of Cholesterol-Lowering Bioactive Peptides: Elucidation of Their Mechanism of Action in HepG2 Cells and Their Trans-Epithelial Transport in Differentiated Caco-2 CellsMartina Bartolomei0Jianqiang Li1Anna Laura Capriotti2Melissa Fanzaga3Lorenza d’Adduzio4Aldo Laganà5Andrea Cerrato6Nadia Mulinacci7Lorenzo Cecchi8Carlotta Bollati9Carmen Lammi10Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, ItalyDepartment of Pharmaceutical Sciences, University of Milan, 20133 Milan, ItalyDepartment of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Pharmaceutical Sciences, University of Milan, 20133 Milan, ItalyDepartment of Pharmaceutical Sciences, University of Milan, 20133 Milan, ItalyDepartment of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Neuroscience, Psychology, Drug and Child Health, Pharmaceutical and Nutraceutical Section, University of Florence, 50019 Florence, ItalyDepartment of Agricultural, Food, Environmental and Forestry Sciences and Technologies, University of Florence, Via Donizetti, 50144 Florence, ItalyDepartment of Pharmaceutical Sciences, University of Milan, 20133 Milan, ItalyDepartment of Pharmaceutical Sciences, University of Milan, 20133 Milan, ItalyThe production of olive oil has important economic repercussions in Mediterranean countries but also a considerable impact on the environment. This production generates enormous quantities of waste and by-products, which can be exploited as new raw materials to obtain innovative ingredients and therefore make the olive production more sustainable. In a previous study, we decided to foster olive seeds by generating two protein hydrolysates using food-grade enzymes, alcalase (AH) and papain (PH). These hydrolysates have shown, both in vitro and at the cellular level, antioxidant and antidiabetic activities, being able to inhibit the activity of the DPP-IV enzyme and modulate the secretion of GLP-1. Given the multifunctional behavior of peptides, both hydrolysates displayed dual hypocholesterolemic activity, inhibiting the activity of HMGCoAR and impairing the PPI of PCSK9/LDLR, with an IC<sub>50</sub> equal to 0.61 mg/mL and 0.31 mg/mL for AH and PH, respectively. Furthermore, both samples restored LDLR protein levels on the membrane of human hepatic HepG2 cells, increasing the uptake of LDL from the extracellular environment. Since intestinal bioavailability is a key component of bioactive peptides, the second objective of this work is to evaluate the capacity of AH and PH peptides to be transported by differentiated human intestinal Caco-2 cells. The peptides transported by intestinal cells have been analyzed using mass spectrometry analysis, identifying a mixture of stable peptides that may represent new ingredients with multifunctional qualities for the development of nutraceuticals and functional foods to delay the onset of metabolic syndrome, promoting the principles of environmental sustainability.https://www.mdpi.com/2072-6643/16/3/371LDLRcholesterol metabolismfood bioactive peptidesmultifunctional peptidesPCSK9 |
| spellingShingle | Martina Bartolomei Jianqiang Li Anna Laura Capriotti Melissa Fanzaga Lorenza d’Adduzio Aldo Laganà Andrea Cerrato Nadia Mulinacci Lorenzo Cecchi Carlotta Bollati Carmen Lammi Olive (<i>Olea europaea</i> L.) Seed as New Source of Cholesterol-Lowering Bioactive Peptides: Elucidation of Their Mechanism of Action in HepG2 Cells and Their Trans-Epithelial Transport in Differentiated Caco-2 Cells Nutrients LDLR cholesterol metabolism food bioactive peptides multifunctional peptides PCSK9 |
| title | Olive (<i>Olea europaea</i> L.) Seed as New Source of Cholesterol-Lowering Bioactive Peptides: Elucidation of Their Mechanism of Action in HepG2 Cells and Their Trans-Epithelial Transport in Differentiated Caco-2 Cells |
| title_full | Olive (<i>Olea europaea</i> L.) Seed as New Source of Cholesterol-Lowering Bioactive Peptides: Elucidation of Their Mechanism of Action in HepG2 Cells and Their Trans-Epithelial Transport in Differentiated Caco-2 Cells |
| title_fullStr | Olive (<i>Olea europaea</i> L.) Seed as New Source of Cholesterol-Lowering Bioactive Peptides: Elucidation of Their Mechanism of Action in HepG2 Cells and Their Trans-Epithelial Transport in Differentiated Caco-2 Cells |
| title_full_unstemmed | Olive (<i>Olea europaea</i> L.) Seed as New Source of Cholesterol-Lowering Bioactive Peptides: Elucidation of Their Mechanism of Action in HepG2 Cells and Their Trans-Epithelial Transport in Differentiated Caco-2 Cells |
| title_short | Olive (<i>Olea europaea</i> L.) Seed as New Source of Cholesterol-Lowering Bioactive Peptides: Elucidation of Their Mechanism of Action in HepG2 Cells and Their Trans-Epithelial Transport in Differentiated Caco-2 Cells |
| title_sort | olive i olea europaea i l seed as new source of cholesterol lowering bioactive peptides elucidation of their mechanism of action in hepg2 cells and their trans epithelial transport in differentiated caco 2 cells |
| topic | LDLR cholesterol metabolism food bioactive peptides multifunctional peptides PCSK9 |
| url | https://www.mdpi.com/2072-6643/16/3/371 |
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